First Analysis of the New FDA Draft on Aseptic Processing

GMP News No. 255

GMP News
28 October 2002

First Analysis of the New FDA Draft
on Aseptic Processing

For many years, the pharmaceutical industry has been waiting for the new FDA "Guideline On Sterile Drug Products Produced By Aseptic Processing." In the meantime, a non-authorised version has been circulating through the pharmaceutical industry since 1998.

At the end of September 2002, FDA finally published an official Preliminary Concept Paper with the title "Sterile Drug Products Produced By Aseptic Processing" as Draft for commenting by the industry.

The document is subdivided into 12 chapters:

  • Introduction
  • Background
  • Scope
  • Buildings and Facilities
  • Personnel Training, Qualification, & Monitoring
  • Components and Containers/Closures
  • Endotoxin Control
  • Time Limitations
  • Process Validation and Equipment Qualification
  • Laboratory Controls
  • Sterility Testing
  • Batch Record Review: Process Control Documentation
  • In addition, at the end of the document you will find the 3 appendices:

  • Aseptic Processing Isolators
  • Blow-Fill-Seal Technology
  • Processing Prior To Filling/Sealing Operations
  • as well as the points References, Relevant Guidance Documents and Draft Glossary.

    On the whole, one can say that - in comparison with the current Guideline - FDA has included topical subjects as well as much-discussed topics of aseptic production. The main chapters of the Guideline are "Process Validation" and "Laboratory Controls" with the subchapter "Environmental Monitoring." Besides, the isolator and blow-fill-seal technologies have found their way into the Guideline.

    As an example, here some notes on "Environmental Monitoring." On the whole, the environmental monitoring programme is assigned a central role. Monitoring data are meant to serve both as quality information on the batch and as trend data for the production environment.

    The chapter is subdivided into the 4 subchapters:

    • General Written Programme
    • Establishing Limits and a Trending Programme
    • Sanitisation Efficacy
    • Monitoring Methods

    The "General Written Program" regulates the points: sampling location, frequency of sampling, when the samples are taken, duration of sampling, sample size, specific sampling equipment and techniques, alert and action limits, appropriate response to deviations from alert or action limits.

    As to the limits and trending programme, importance is given to the individual results. The calculation of mean values is considered as critical. Trending is to be divided into near-term and long-term trends. Whenever a result is at the alert or action limit, measures have to be taken. In case atypical microorganisms (which ones?) are detected, further investigations have to be conducted. The responsible managers have to be informed regularly about trends and investigations.

    As regards sanitisation efficacy, the document requires that the sporicidal efficacy of disinfectants is proved and that these agents are applied regularly. Another requirement is that sanitisation efficacy is proved regularly within the framework of the monitoring programme.

    Under "Monitoring Methods" you can find surface monitoring as well as active and passive air monitoring. The efficacy of passive monitoring by means of petri dishes has to be proved (effect of the desiccation of the plates on the recovery rate of microorganisms).

    Surely, some of the requirements, especially in the chapter "Environmental Monitoring", may (by far) overshoot the mark and give rise to uncertainty. This is one of the reasons why the pharmaceutical industry should take this Draft seriously and seize the opportunity to make contributions to the incipient discussion.

    CONCEPT HEIDELBERG and well-known European speakers present the Draft Guideline "Sterile Drug Products Produced by Aseptic Processing" to the participants of the European Aseptic Conference 2002, taking place in Barcelona, Spain, on 26-27 November, and offer a forum for discussing the presented requirements to interested persons from pharmaceutical industry and supplier firms at the event.

    Dr Andreas Mangel

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